Biodegradable polymeric endoluminal sealing process, apparatus and polymeric product for use therein

ABSTRACT

A process for paving or sealing the interior surface of a tissue lumen by entering the interior tissue lument and applying a polymer to the interior surface of the tissue lumen. This is accomplished using a catheter which delivers the polymer to the tissue lument and causes it to conform to the interior surface of the lumen. The polymer can be delivered to the lumen as a monomer or prepolymer solution, or as an at least partially preformed layer on an expansible member.

This application is a continuation application under 37 CFR 1.62 ofprior application Ser. No. 07/651,346, filed as PCT/US89/03593, Feb. 23,1989, now abandoned, which in turn is a continuation-in-part ofapplication Ser. No. 07/593,302, filed on Oct. 3, 1990, now abandoned,and a continuation-in-part of application Ser. No. 07/235,998, filed onAug. 24, 1988, now abandoned.

BACKGROUND OF THE INVENTION

This invention relates to a novel method for the in vivo paving andsealing of the interior of organs or organ components and other tissuecavities, and to apparatus and partially pre-formed polymeric productsfor use in this method. The tissues involved may be those organs orstructures having hollow or tubular geometry, for example blood vesselssuch as arteries or veins, in which case the polymeric products aredeposited within the naturally occurring lumen. Alternatively, thetissue may be a normally solid organ in which a cavity has been createdeither as a result of an intentional surgical procedure or an accidentaltrauma. In this case, the polymeric product is deposited in the lumen ofthe cavity.

Often times, the hollow or tubular geometry of organs has functionalsignificance such as in the facilitation of fluid or gas transport(blood, urine, lymph, oxygen or respiratory gases) or cellularcontainment (ova, sperm). Disease processes may affect these organs ortheir components by encroaching upon, obstructing or otherwise reducingthe cross-sectional area of the hollow or tubular elements.Additionally, other disease processes may violate the native boundariesof the hollow organ and thereby affect its barrier function and/orcontainment ability. The ability of the organ or structure to properlyfunction is then severely compromised. A good example of this phenomenacan be seen by reference to the coronary arteries.

Coronary arteries, or arteries of the heart, perfuse the actual cardiacmuscle with arterial blood. They also provide essential nutrients andallow for removal of metabolic wastes and for gas exchange. Thesearteries are subject to relentless service demands for continuous bloodflow throughout the life of the patient.

Despite their critical life supporting function, coronary arteries areoften subject to attack through several disease processes, the mostnotable being atherosclerosis or hardening of the arteries. Throughoutthe life of the patient, multiple factors contribute to the developmentof microscopic and/or macroscopic vascular lesions known as plaques.

The development of a plaque lined vessel typically leads to an irregularinner vascular surface with a corresponding reduction of vesselcross-sectional area. The progressive reduction in cross-sectional areacompromises flow through the vessel. For example, the effect on thecoronary arteries, is a reduction in blood flow to the cardiac muscle.This reduction in blood flow, with corresponding reduction in nutrientand oxygen supply, often results in clinical angina, unstable angina ormyocardial infarction (heart attack) and death. The clinicalconsequences of the above process and its overall importance are seen inthat atherosclerotic coronary artery disease represents the leadingcause of death in the United States today.

Historically, the treatment of advanced atherosclerotic coronary arterydisease i.e. beyond that amenable to therapy via medication alone,involved cardio-thoracic surgery in the form of coronary artery bypassgrafting (CABG). The patient is placed on cardio-pulmonary bypass andthe heart muscle is temporarily stopped. Repairs are then surgicallyaffected on the heart in the form of detour conduit grafted vesselsproviding blood flow around obstructions. While CABG has been perfectedto be quite effective it carries with it inherent surgical risk andrequires a several week, often painful recouperation period. In theUnited States alone approximately 150-200 thousand people are subjectedto open heart surgery annually.

In 1977 a major advance in the treatment of atherosclerotic coronaryartery disease occurred with the introduction of a technique known asPercutaneous Transluminal Coronary Angioplasty (PTCA). PTCA involves theretrograde introduction, from an artery in the arm or leg, up to thearea of vessel occlusion, of a catheter with a small dilating balloon atits tip. The catheter is snaked through the arteries via directfluoroscopic guidance and passed across the luminal narrowing of thevessel. Once in place, the catheter balloon is inflated to severalatmospheres of pressure. This results in "cracking", "plastic" orotherwise mechanical deformation of the lesion or vessel with asubsequent increase in the cross-sectional area. This in turn reducesobstruction, and trans-lesional pressure gradients and increases bloodflow.

PTCA is an extremely effective treatment with a relatively low morbidityand is rapidly becoming a primary therapy in the treatment ofatherosclerotic coronary disease throughout the United States and theworld. By way of example, since its introduction in 1977, the number ofPTCA cases now exceeds 150,000 per annum in the United States and, forthe first time in 1987, surpassed the number of bypass operationsperformed. Moreover, as a result of PTCA, emergency coronary arterybypass surgery is required in less than four percent of patients.Typically, atherosclerosis is a diffuse arterial disease processexhibiting simultaneous patchy involvement in several coronary arteries.Patients with this type of widespread coronary involvement, whilepreviously not considered candidates for angioplasty, are now beingtreated due to technical advances and increased clinical experience.

Despite the major therapeutic advance in the treatment of coronaryartery disease which PTCA represents, its success has been hampered bythe development of vessel renarrowing or reclosure post dilation. Duringa period of hours or days post procedure, significant total vesselreclosure may develop in up to 10% of cases. This is referred to as"abrupt reclosure". However, the more common and major limitation ofPTCA, is the development of progressive reversion of the vessel to itsclosed condition, negating any gains achieved from the procedure.

This more gradual renarrowing process is referred to as "restenosis."Post-PTCA follow-up studies report a 10-50% incidence (averagingapproximately 30%) of restenosis in cases of initially successfulangioplasty. Studies of the time course of restenosis have shown that itis typically an early phenomenon, occurring almost exclusively withinthe six months following an angioplasty procedure. Beyond this six-monthperiod, the incidence of restenosis is quite rare. Despite recentpharmacologic and procedural advances, little success has been achievedin preventing either abrupt reclosure or restenosis post-angioplasty.

Restenosis has become even more significant with the increasing use ofmulti-vessel PTCA to treat complex coronary artery disease. Studies ofrestenosis in cases of multi-vessel PTCA reveal that after multi-lesiondilatation, the risk of developing at least one recurrent coronarylesion range from 26% to 54% and appears to be greater than thatreported for single vessel PTCA. Moreover, the incidence of restenosisincreases in parallel with the severity of the pre-angioplasty vesselnarrowing. This is significant in light of the growing use of PTCA totreat increasingly complex multi-vessel coronary artery disease.

The 30% overall average restenosis rate has significant costs includingpatient morbidity and risks as well as medical economic costs in termsof follow-up medical care, repeat hospitalization and recurrentcatherization and angioplasty procedures. Most significantly, prior torecent developments, recurrent restenosis following multiple repeatangioplasty attempts could only be rectified through cardiac surgerywith the inherent risks noted above.

In 1987 a mechanical approach to human coronary artery restenosis wasintroduced by Swiss investigators referred to as, "IntracoronaryStenting". An intracoronary stent is a tubular device made of fine wiremesh, typically stainless steel. The Swiss investigators utilized astent of the Wallsten design as disclosed and claimed in U.S. Pat. No.4,655,771. The device can be configured in such a manner as to be of lowcross-sectional area. In this "low profile" condition the mesh is placedin or on a catheter similar to those used for PTCA. The stent is thenpositioned at the site of the vascular region to be treated. Once inposition, the wire mesh stent is released and allowed to expand to itsdesired cross-sectional area generally corresponding to the internaldiameter of the vessel. Similar solid stents are also disclosed in U.S.Pat. No. 3,868,956 to Alfidi et al.

The metal stent functions as a permanent intravascular scaffold. Byvirtue of its material properties, the metal stent provides structuralstability and direct mechanical support to the vascular wall. Stents ofthe Wallsten design are self-expanding due to their helical "spring"geometry. Recently, U.S. investigators introduced slotted steel tubesand extended spring designs. These are deployed through application ofdirect radial mechanical pressure conveyed by a balloon at the cathetertip. Such a device and procedure are claimed in U.S. Pat. No. 4,733,665to Palmaz. Despite the significant limitations and potentially seriouscomplications discussed below, this type of stenting has been successfulwith an almost 100% acute patency rate and a marked reduction in therestenosis rate.

The complications associated with permanent implants such as the Palmazdevice result from both the choice of material, i.e., metal or stainlesssteel, as well as the inherent design deficiencies in the stentingdevices. The major limitation lies in the permanent placement of anon-retrivable, non-degradable, foreign body in a vessel to combatrestenosis which is predominately limited to the six-month time periodpost-angioplasty. There are inherent, significant risks common to allpermanent implant devices. Moreover, recent studies have revealed thatatrophy of the media, the middle arterial layer of a vessel, may occuras a specific complication associated with metal stenting due to thecontinuous lateral expansile forces exerted after implantation.

These problems are even more acute in the placement of a permanentmetallic foreign body in the vascular tree associated with the cardiacmuscle. Coronary arteries are subjected to the most extreme servicedemands requiring continuous unobstructed patency with unimpeded flowthroughout the life of the patient. Failure in this system will lead tomyocardial infarction (heart attack) and death. In addition, thetorsional and other multi-directional stresses encountered in the heartdue to its continuous oscillatory/cyclic motion further amplifies therisks associated with a permanent, stiff metallic intra-arterial implantin the coronary bed.

It has been observed that, on occasion, recurrent intravascularnarrowing has occurred post-stent placement in vessels during a periodof several weeks to months. Typically, this occurs "peri-stent", i.e.,immediately up or down stream from the stent. It has been suggested thatthis may relate to the significantly different compliances of the vesseland the stent, sometimes referred to as "compliance mismatch". Asidefrom changes in compliance another important mechanism leading toluminal narrowing above and below the stent may be the changes in shearforces and fluid flows encountered across the sharp transitions of thestent-vessel interface. Further supporting evidence has resulted fromstudies of vascular grafts which reveal a higher incidence of thrombosisand eventual luminal closure also associated with significant compliancemismatch.

To date known stent designs, i.e. tubular, wire helical or spring,scaffold design have largely been designed empirically withoutconsideration or measurement of their radial stiffness. Recent studiesmeasuring the relative radial compressive stiffness of known wirestents, as compared to physiologically pressurized arteries, have foundthem to be much stiffer than the actual biologic tissue. These studieslend support to the concept of poor mechanical biocompatibility ofcurrently available stents.

Conventional metal stenting is severely limited since it is devicedependent and necessitates a myriad of individual stents as well asmultiple deployment catheters of varying lengths and sizes toaccommodate individual applications. Additionally, metal stents providea relatively rigid nonflexible structural support which is not amenableto a wide variety of endoluminal geometries, complex surfaces, luminalbends, curves or bifurcations.

These identified risks and limitations of metal stents have severelylimited their utility in coronary artery applications. As of 1988, apartial self-imposed moratorium exists in the use of helical metalstents to treat human coronary artery diseases. Presently in the UnitedStates a spring-like wire coil stent has been approved only for shortterm use as an emergency device for patients with irreparably closedcoronary arteries following failed PTCA while in transit to emergencybypass surgery. An alternative to the use of stents has now been foundwhich has broad applications beyond use in coronary artery applicationsfor keeping hollow organs open and in good health.

SUMMARY OF THE INVENTION

The present invention provides a solution to the problem of restenosisfollowing angioplasty, without introducing the problems associated withmetal stents. Specifically, the invention provides a novel method forendoluminal paving and sealing (PEPS) which involves application of apolymeric material to the interior surface of the involved blood vessel.In accordance with this method, a polymeric material, either in the formof a monomer or prepolymer solution or as an at least partiallypre-formed polymeric product, is introduced into the lumen of the bloodvessel and positioned at the point of the original stenosis. Thepolymeric product is then reconfigured to conform to and maintainintimate contact with the interior surface of the blood vessel such thata paving and sealing coating is achieved.

The PEPS approach is not limited to use in connection with restenosis,however, and can also be effectively employed in any hollow organ toprovide local structural support, a smooth surface, improved flow andsealing of lesions. In addition, the polymeric paving and sealingmaterial may incorporate therapeutic agents such as drugs, drugproducing cells, cell regeneration factors or even progenitor cells ofthe same type as the involved organ or histologically different toaccelerate healing processes. Such materials with incorporatedtherapeutic agents may be effectively used to coat or plug surgically ortraumatically formed lumens in normally solid organs as well as thenative or disease generated lumens of hollow or tubular organs.

For use in these applications, the present invention provides at leastpartially preformed polymeric products. These products may have any of avariety of physical shapes and sizes in accordance with the particularapplication. The invention also provides apparatus specially adapted forthe positioning of the polymeric material, these including partiallypre-formed polymeric products, at the interior surface of an organ andfor the subsequent chemical or physical reconfiguration of the polymericmaterial such that it assumes a desired molded or customized finalconfiguration.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows an amorphous geometry of the PEPS polymer coating beforeand after deployment;

FIG. 2 shows a stellate geometry of the PEPS polymer coating before andafter deployment;

FIG. 3 shows a linear leathered polymer strip applied to "one" wallbefore and after deployment;

FIG. 4 shows a large patch of sprayed on polymer material before andafter deployment;

FIG. 5 shows a porous tubular form geometry before and after deployment;

FIG. 6 shows a spot geometry of the PEPS process before and afterdeployment;

FIG. 7 shows a spiral form application of the PEPS process before andafter deployment;

FIG. 8 shows an arcuate (radial, arc) patch geometry of the PEPS polymerbefore and after deployment;

FIG. 9 shows a process for using PEPS to treat an artificially createdtissue lumen;

FIGS. 10a-e show various embodiments of dual lumen catheters accordingto the invention;

FIGS. 11a-d show various embodiments of expansile members useful incatheters according to the invention;

FIGS. 12a-g depict various three-lumen catheters according to theinvention;

FIGS. 13a-h depict various four-lumen catheters according to theinvention;

FIG. 14 shows five lumen catheters according to the invention;

FIGS. 15a-b depict a six-lumen catheter according to the invention;

FIG. 16 shows seven lumen catheters according to the invention;

FIG. 17 shows a distal occlusion catheter and a polymer deliverycatheter in a vessel;

FIG. 18 shows in cross-section a polymeric sleeve before insertion in ablood vessel; the sleeve after insertion in the vessel and afterexpansion;

FIG. 19 is a cross-sectional comparison of an initial polymeric sleeveand an expanded polymeric sleeve.

FIGS. 20a-e depict enmeshed discontinuous polymeric material arrayed ona catheter having a retractable sheath; and

FIGS. 21a-c depict various embodiments of catheters having apertures forpolymer delivery to a tissue lumen.

DETAILED DESCRIPTION OF THE INVENTION

In general, PEPS involves the introduction of a polymeric material intoa selected location within a lumen in tissue, i.e. an organ, an organcomponent or cavernous component of an organism, and the subsequentreconfiguration of the polymeric material to form a sealing in intimateand conforming contact with, or paving the interior surface. As usedherein, the term "sealing" or "seal" means a coating of sufficiently lowporosity that the coating serves a barrier function. The term "paving"refers to coatings which are porous or perforated. By appropriateselection of the polymeric material employed and of the configuration ofthe coating or paving, PEPS provides a unique customizable process,which can be utilized as a given biological or clinical situationdictates.

The basic requirements for the polymeric material to be used in the PEPSprocess are biocompatibility and the capacity to be chemically orphysically reconfigured under conditions which can be achieved in vivo.Such reconfiguration conditions may involve heating, cooling, mechanicaldeformation, e.g., stretching, or chemical reactions such aspolymerization or crosslinking.

Suitable polymeric materials for use in the invention include polymersand copolymers of carboxylic acids such as glycolic acid and lacticacid, polyurethanes, polyesters such as poly(ethylene terephthalate),polyamides such as nylon, polyacrylonitriles, polyphosphazines,polylactones such as polycaprolactone, and polyanhydrides such as polybis(p-carboxyphenoxy)propane anhydride! and other polymers or copolymerssuch as polyethylene, polyvinyl chloride and ethylene vinyl acetate.

Other bioabsorbable polymers could also be used either singly or incombination, or such as homopolymers and copolymers ofdelta-valerolactone, and p-dioxanone as well as their copolymers withcaprolactone. Further, such polymers can be crosslinked withbis-caprolactone.

Preferably PEPS utilizes biodegradable polymers, with specificdegradation characteristics to provide sufficient lifespan for theparticular application. As noted above, a six month lifespan is probablysufficient for use in preventing restenosis; shorter or longer periodsmay be appropriate for other therapeutic applications.

Polycaprolactone as disclosed and claimed in U.S. Pat. No. 4,702,917 toSchindler, incorporated herein by reference, is a highly suitablebioabsorbable polymer for use in the PEPS process, particularly forprevention of restenosis. Polycaprolactone possesses adequate mechanicalstrength being mostly crystalline even under quenching conditions.Despite its structural stability, polycaprolactone is much less rigidthan the metals used in traditional stenting. This minimizes the risk ofacute vessel wall damage from sharp or rough edges. Furthermore, oncepolycaprolactone has been deployed, its crystalline structure willmaintain a constant outside diameter. This eliminates the risks oftenassociated with known helical or spring metal stents which after beingexpanded in vivo have a tendency to further expand exerting increasingpressure on the vessel wall.

The rate of bioabsorption of polycaprolactone is ideal for thisapplication. The degradation process of this polymer has been wellcharacterized with the primary degradation product being nonparticulate,nontoxic, 6-hydroxy hexanoic acid of low acidity. The time ofbiodegradation of polycaprolactone can be adjusted through the additionof various copolymers.

Polycaprolactone is a preferred polymer for use in the PEPS processbecause it has attained favorable clinical acceptability and is in theadvanced stages of FDA approval. Polycaprolactone has a crystallinemelting point of 60° C. and can be deployed in vivo via a myriad oftechniques which facilitate transient heating and varying degrees ofmechanical deformation or application as dictated by individualsituations. This differs markedly from other bioabsorbable polymers suchas polyglycolide and polylactide which melt at much higher temperaturesof 180° C. and pose increased technical constraints as far as thedelivery system affording polymer sculpting without deleterious tissueexposure to excessive temperatures or mechanical forces.

Polyanhydrides have been described for use as drug carrier matrices byLeong et al., J. Biomed. Mat. Res. 19, 941-955 (1985). These materialsfrequently have fairly low glass transition temperatures, in some casesnear normal body temperature, which makes them mechanically deformablewith only a minimum of localized heating. Furthermore, they offererosion times varying from several months to several years depending onparticular polymer selected.

The polymeric materials may be applied in custom designs, with varyingthicknesses, lengths, and three-dimensional geometries (e.g. spot,stellate, linear, cylindrical, arcuate, spiral) to achieve varyingfinished geometries as depicted in FIGS. 1-8. Further, PEPS may be usedto apply polymer to the inner surfaces of hollow, cavernous, or tubularbiological structures (whether natural or artificially formed) in eithersingle or multiple polymer layer configurations. PEPS may also be used,where appropriate, to occlude a tissue lumen completely.

The polymeric material used in PEPS can be combined with a variety oftherapeutic agents for on-site delivery. Examples for use in coronaryartery applications are anti-thrombotic agents, e.g., prostacyclin andsalicylates, thrombolytic agents e.g. streptokinase, urokinase, tissueplasminogen activator (TPA) and anisoylated plasminogen-streptokinaseactivator complex (APSAC), vasodilating agents i.e. nitrates, calciumchannel blocking drugs, anti-proliferative agents i.e. colchicine andalkylating agents, intercalating agents, growth modulating factors suchas interleukins, transformation growth factor β and congeners ofplatelet derived growth factor, monoclonal antibodies directed againstgrowth factors, anti-inflammatory agents, both steroidal andnon-steroidal, and other agents which may modulate vessel tone,function, arteriosclerosis, and the healing response to vessel or organinjury post intervention. In applications where multiple polymer layersare used different pharmacological agents could be used in differentpolymer layers. Moreover, PEPS may be used to effect pharmaceuticaldelivery locally within the vessel wall, i.e. media.

The polymeric material in accordance with the invention may also haveincorporated in it living cells to serve any of several purposes. Forexamples, the cells may be selected, or indeed designed using principlesof recombinant DNA technology, to produce specific agents such as growthfactors. In such a way, a continuously regenerating supply of atherapeutic agent may be provided without concerns for stability,initial overdosing and the like.

Cells incorporated in the polymeric material may also be progenitorcells corresponding to the type of tissue in the lumen treated or othercells providing therapeutic advantage. For example, liver cells might beimplanted in the polymeric material within a lumen created in the liverof a patient to facilitate regeneration and closure of that lumen. Thismight be an appropriate therapy in the case where scar tissue or otherdiseased, e.g. cirrhosis, fibrosis, cystic disease or malignancy, ornon-functional tissue segment has formed in the liver or other organ andmust be removed. The process of carrying out such treatment, shownschematically in FIG. 9, involves first inserting a catheter 91 into alumen 92 within a diseased organ segment 93. The lumen 92 can be anative vessel, or it can be a man-made lumen, for example a cavityproduced by a laser. The catheter 91 is used to introduce a polymericplug 94 into the lumen 92. The catheter is then removed, leaving theplug 94 in place to act as a focus for new growth stemming from cellsimplanted along with the polymeric plug 94. If the desire is for a moretubular structure, the plug 94 can be appropriately reconfigured.

Optional additions to the polymeric material such as barium, iodine ortantalum salts for X-ray radio-opacity allow visualization andmonitoring of the coating.

The technique of PEPS preferably involves the percutaneous applicationof a polymeric material, preferably a biodegradable polymer such aspolycaprolactone, either alone or mixed with other biodegradablepolymeric materials, which may optionally contain various pharmaceuticalagents for controlled sustained release of the pharmaceutical or forselective soluble factor adsorption and trapping. The polymeric materialis typically applied to the inside of an organ surface employingcombined thermal and mechanical means to manipulate the polymericmaterial. Although capable of being used during surgery, PEPS willgenerally be applied without the need for a surgical procedure usingsome type of catheter, for example novel modifications of the knowncatheter technology described above for (PTCA). PEPS is preferablyapplied using a single catheter with multiple balloons and lumens. Thecatheter should be of relatively low cross-sectional area. Typically along thin tubular catheter manipulated using fluoroscopic guidance canaccess deep into the interior of organ or vascular areas.

The polymer may be deployed in the interior of the vessel or organ fromthe surface or tip of the catheter. Alternatively, the polymer could bepositioned on a balloon such as that of a standard angioplasty ballooncatheter. Additionally, the polymer could be applied by spraying,extruding or otherwise internally delivering the polymer via a longflexible tubular device consisting of as many lumens as a particularapplication may dictate.

The simplest PEPS coating is a continuous coating over a designatedportion of a tissue lumen. Such a coating can be applied with a simpletwo lumen catheter such as those shown in FIGS. 10a-10c. Looking firstto FIG. 10a, a suitable catheter is formed from a tubular body 100having a proximal end 101 and a distal end 102. The interior of thetubular body 100 is divided into two conduits 103 and 104 which extendfrom the proximal end 101 to apertures 105 and 106 in the tubular body.(FIGS. 10b and 10c) Conduits 103 and 104 thus connect apertures 105 and106 with the proximal end 101 of the tubular body 100 to allow fluidflow therebetween. The proximal ends of conduits 103 and 104 arepreferably equipped with connectors 108 which allow connection withfluid supplies. Pressure connectors such as Luer® locks are suitable.

The catheter may also include markers 109 in one or more locations toaid in locating the catheter. These markers can be, for example,fluoroscopic radio-opaque bands affixed to the tubular body 100 by heatsealing.

The catheter shown in FIGS. 10b and 10c has an expansile member in theform of an inflatable balloon 107 disposed over the distal aperture 105.In use, an at least a partially preformed polymeric layer or partiallayer is positioned over the balloon 107 and the catheter is insertedinto an appropriate position in the tissue lumen. Fluid flow throughconduit 103 will cause the balloon 107 to inflate, stretch and deformthe polymer layer until it comes into contact with the walls of thetissue lumen. The other aperture 106 and conduit 104 are used to controlthe reconfiguration of the polymeric sleeve, for example by supplying aflow of heated liquid to soften the sleeve and render it more readilystretchable or to stimulate polymerization of a partially polymerizedsleeve.

Variations on this basic two lumen catheter can be made, examples ofwhich are shown in FIGS. 10d and 10e. For example FIG. 10d has ashapable wire affixed to the tip of the catheter to aid in insertion anda traumatic and directed passage through the organism, i.e. to act as aguide wire. In FIG. 10e, the expansile member is incorporated as part ofthe tubular body as a continuous element, preferably a unitary element.In this case, the distal tip 107a of the catheter expands in response tofluid flow in conduit 103. Conduit 104 can be formed by bonding in or onthe extruded catheter body a piece of the same or different material ina tubular form. This type of design can also be used in more complicatedmulti-lumen catheters discussed below.

The polymeric material may take the form of a sleeve designed to bereadily insertable along with the catheter into the tissue lumen, andthen to be deployed onto the wall of the lumen to form the coating. Thisdeployment can be accomplished by inflating a balloon, such as balloon107 using fluid flow through conduit 103. Inflation of balloon 107stretches the polymeric sleeve causing it to press against the walls ofthe tissue lumen and acquire a shape corresponding to the lumen wall.This shape is then fixed, and the cather removed leaving behind apolymeric paving or seal on the lumen wall.

The process of fixing the shape of the polymeric material can beaccomplished in several ways, depending on the character of the originalpolymeric material. For example, a partially polymerized material can beexpanded using the balloon after which the conditions are adjusted suchthat polymerization can be completed, e.g., by increasing the localtemperature or providing UV radiation through an optical fiber. Atemperature increase might also be used to soften a fully polymerizedsleeve to allow expansion and facile reconfiguration and local molding,after which it would "freeze" in the expanded position when the heatsource is removed. Of course, if the polymeric sleeve is a plasticmaterial which will permanently deform upon stretching (e.g.,polyethylene, polyethylene terephthalate, nylon or polyvinyl chloride),no special fixation procedure is required.

As depicted in FIG. 10b, local heating can be provided by a flow ofheated liquid directly into the tissue lumen. Thermal control can alsobe provided, however, using a fluid flow through or into the expansilemember or using a "leaky" partially perforated balloon such thattemperature control fluid passes through the expansile member, or usingelectrical resistive heating using a wire running along the length ofthe catheter body in contact with resistive heating elements. This typeof heating element can make use of DC or radiofrequency (RF) current orexternal RF or microwave radiation. Other methods of achievingtemperature control can also be used, including laser heating using aninternal optical fiber (naked or lensed) or thermonuclear elements.

In addition to the smooth shape shown in FIG. 10, the balloon used toconfigure the polymer can have other surface shapes for formation of thecoatings to provide specific polymeric deployment patterns. For example,the balloon may be a globular shape intended for deployment from the tipof a catheter device. (FIG. 11a) Such an arrangement would be preferredwhen the paving operation is being carried out in a cavity as opposed toa tubular organ. The balloon might also be thickened at the ends (FIG.11b) or substantially helical (FIG. 11c) providing a variation incoating thickness along the length of the paved or sealed area. Such aconfiguration might prove advantageous in the case where additionalstructural support is desired and to provide a tapered edge to minimizeflow disruption. Variations in coating thickness which provide ribsrunning the length of the tissue lumen might be achieved using astellate balloon (FIG. 11d). This type of polymer coating would beuseful in the case where additional structural support is desirouscombined with more continuous flow properties. In addition balloon shapemay facilitate insertion in some cases.

Variations in the ultimate configuration of the PEPS coating can also beachieved by using more complex deployments of the polymer on theexpansile member. For example, the polymer can be in the form of aperforated tubular sleeve, a helical sleeve or in the form ofdiscontinuous members of various shapes. These may be affixed to theexpansile member directly, for example with an adhesive or by suctionthrough perforations and the like, or to an overcoating such asdissolvable gauze-like or paper sheath (i.e. spun saccharide) or held inplace by a retractable porous sheath which will be removed with thecatheter after application.

For example, FIG. 20(a) shows an array of polymer dots. These dots areenmeshed in a dissolvable mesh substrate FIG. 20(b) which in turn iswrapped around the expansile member 107 of a catheter according to theinvention (FIG. 20c). An exemplary two lumen catheter is shown in FIG.20d (numbered as in FIG. 10b) where a retractable sheath 205 surroundsthe polymer dots 206 for insertion. When the catheter reaches theapplication site, the sheath 205 is retracted (FIG. 20e) and the balloon107 expanded.

It will be recognized, that the catheter depicted in FIG. 20d representsa minimalist approach to PEPS catheter design, and that additionallumens may be included within the catheter body to provide conduits forinflation of positioning balloons, optical fibers, additional polymermolding balloons, temperature control means, and passage of steering orguide wires or other diagnostic devices, e.g. ultrasound catheter, ortherapeutic devices such as atherectomy catheter or other lesionmodifying device. For example, three lumen catheters (FIGS. 12a-12d)four lumen catheters (FIGS. 13a-13h), five lumen catheters (FIGS. 14aand 14b), six lumen catheters (FIGS. 15a and 15b) and seven lumencatheters (FIGS. 16a and 16b) might be employed. A retractable sheathmay also be provided which extends over the polymer during insertion toprevent premature separation of the polymer from the catheter. Inaddition, catheters may have telescoping sections such that the distancebetween the occluding balloons can be varied.

Looking for example at the six lumen catheters in FIGS. 15a and 15b, twopositioning balloons 150 and 151, both connected to conduit 152.Positioning balloons 150 and 151 serve to fix the position of thetubular body 100 within a tissue lumen and isolate the portion of thetissue lumen between them where the PEPS coating will be applied.Expansile member 153 is provided with circulating flow via conduits 154and 155. This can be used to provide temperature control to the isolatedportion of the tissue lumen, as well as acting to configure thepolymeric coating formed by expanding a polymeric sleeve and otherdeployed form fitted over expansile member 153. In the catheter shown inFIG. 15b, a temperature control solution or a therapeutic solution isadvantageous provided through conduit 156, with conduit 157 acting as adrain line (or vice versa) to allow flow of fluid through the isolatedportion of the tissue lumen ("superfusion"). Such a drain line is notrequired, however, and a simple infusion cather could omit one of theconduits 156 or 157 as in the five lumen designs of FIGS. 14a and 14b.The sixth conduit 158 is also optional, but can be advantageously usedfor guide wires, diagnostic or therapeutic device passage, or distalfluid perfusion. If conduit 158 has an aperture proximal to balloon 151,it can be used as a by-pass conduit for passive perfusion duringocclusion.

The incorporation in the catheter of positioning balloons which occludea section of the tissue lumen makes it possible to utilize solutions ofmonomers or prepolymers and form the coating in situ. Looking forexample at four lumen catheters shown in FIG. 13b, an isolation zone iscreated by inflating balloons 131 and 132 so that they press against thetissue lumen. While expansile member 133 could be used to deform apolymeric sleeve or other deployment form, it can also be used to definethe size and environmental conditions (e.g. temperature) of the lumenregion.

Application of the polymeric material may be accomplished by extruding asolution of monomers or prepolymers through the aperture 134 to coat orfill the tissue lumen. The formation of a polymer coating can becontrolled by introducing crosslinking agents or polymerizationcatalysts together with the monomer or prepolymer solution and thenaltering the conditions such that polymerization occurs. Thus, a flow ofheated fluid into expansile member 133 can increase the localtemperature to a level sufficient to induce or acceleratepolymerization. Alternatively, the monomer/prepolymer solution might beintroduced cold, with metabolic temperature being sufficient to inducepolymerization. The other aperture 135 acts as a drain line insuperfusion applications.

The polymeric material can be introduced to the tissue lumen through asimple aperture in the side of the tube as shown in FIG. 21a, or througha raised aperture (FIG. 21d). A shaped nozzle which is extendable awayfrom the surface of the tubular body (FIG. 21e) can also be used. Thematerial can be extruded through, or it can be subjected to flowrestriction to yield a spray application. This flow restriction can beadjustable to control the spray. In addition, localized acceleration atthe tip of the nozzle can be used, for example, via a piezoelectricelement to provide sprayed application.

The catheters bodies for use in this invention can be made of any knownmaterial, including metals, e.g. steel, and thermoplastic polymers.Occluding balloons may be made from compliant materials such as latex orsilicone, or non-compliant materials such as polyethyleneterephthalate(PET). The expansile member is preferably made from non-compliantmaterials such as PET, PVC, polyethylene or nylon. The expansile membermay optionally be coated with materials such as silicones,polytetra-fluoroethylene (PTFE), hydrophilic materials like hydratedhydrogels and other lubricious materials to aid in separation of thepolymer coating.

In addition to arteries, i.e. coronary, femeroiliac, carotid andvertebro-basilar, the PEPS process may be utilized for otherapplications such as paving the interior of veins, ureters, urethrae,bronchi, biliary and pancreatic duct systems, the gut, eye and spermaticand fallopian tubes. The sealing and paving of the PEPS process can alsobe used in other direct clinical applications even at the coronarylevel. These include but are not limited to the treatment of abruptvessel reclosure post PCTA, the "patching" of significant vesseldissection, the sealing of vessel wall "flaps", i.e. secondary tocatheter injury or spontaneously occurring, the sealing of aneurysmalcoronary dilations associated with various arteritidies. Further, PEPSprovides intra-operative uses such as sealing of vessel anostomosesduring coronary artery bypass grafting and the provision of a bandagedsmooth polymer surface post endarterectomy.

The unique pharmaceutical delivery function of the PEPS process may bereadily combined with "customizable" deployment geometry capabilities toaccommodate the interior of a myriad of complex organ or vesselsurfaces. Most importantly, this customized geometry can be made fromstructurally stable yet biodegradable polymers. The ability to tailorthe external shape of the deployed polymer through melted polymer flowinto uneven surface interstices, while maintaining a smooth interiorsurface with good flow characteristics, will facilitate betterstructural support for a variety of applications including eccentriccoronary lesions which by virtue of their geometry are not well bridgedwith conventional metal stents.

As noted above, the polymer substrate used in PEPS may be fashioned, forexample, out of extruded tubes of polycaprolactone and/or copolymers.The initial predeployment design and size of the polymer sleeve will bedictated by the specific application based upon the final deployedphysical, physiological and pharmacological properties desired.

For coronary artery application, predeployment tubes of about 10 to 20mm in length and about 1 to 2 mm in diameter would be useful. Theinitial wall thickness of the resulting in vivo polymer layer may bevaried depending upon the nature of the particular application. Ingeneral coating procedures require polymer layers of about 0.005 mm to0.50 mm while layers which are designed to give structural support canvary from 0.05 mm to 5.0 mm.

The polymer tube walls may be processed prior to insertion with eitherlaser or chemical etching, pitting, slitting or perforation dependingupon the application. In addition, the shape of any micro (10 nm to 1μm) or macro (>1 μm up to about 15 μm) perforation may be furthergeometrically modified to provide various surface areas on the innerversus outer seal surface. The surfaces of the predeployed polymer maybe further modified with bound, coated, or otherwise applied agents,i.e., cyanoacrylates or biological adhesives such as those derived fromfungal spores, the sea mussel or autologous fibrinogen adhesive derivedfrom blood.

For PEPS applications involving the coronary arteries, the polymer tubes(if in an initial tubular configuration), should preferably haveperforations or pores, of a size dictated by the particular application.This will ensure a symmetric expansion of the encasing polymericsealant. By using a fragmented tubular polymer surface withcorresponding expansions along predicted perforations (i.e., the slots)a significant mechanical stabililty is provided. In addition, thisminimizes the amount of foreign material placed within the vessel.

Depending upon the polymer and pharmaceutical combination and theconfiguration, PEPS may be used to coat or bandage the organ innersurface with a thin adhesive partitioning polymer film or layer of about0.005 mm to 0.50 mm. Biodegradable polymers thus applied to an internalorgan or vessel surface will act as an adherent film "bandage." Thisimproved surface, with desirable rheologic and adherence properties,facilitates improved fluid or gas transport in and through the body orlumen of the vessel or hollow organ structure and acts to reinstateviolated native surfaces and boundaries.

The ultimate in vivo deployed geometry of the polymer dictates the finalfunction of the polymer coating. The thinner applications allow thepolymer film to function as a coating, sealant and/or partitioningbarrier, bandage, and drug depot. Complex internal applications ofthicker layers of polymer, such as intra-vessel or intra-luminalapplications, may actually provide increased structural support anddepending on the amount of polymer used in the layer may actually servein a mechanical role to maintain vessel or organ potency.

For example, lesions which are comprised mostly of fibromuscularcomponents have a high degree of visco-elastic recoil. These lesionswould require using the PEP process to apply an intraluminal coating ofgreater thickness and extent so as to impart more structural stabilitythereby resisting vessel radial compressive forces. The PEPS process inthis way provides structural stability and is generally applicable forthe maintenance of the intraluminary geometry of all tubular biologicalorgans or substructure. It may be used in this way following thetherapeutic return of normal architecture associated with either balloondilation (PTCA), atherectomy, lesion spark, thermal or other mechanicalerosion, "G-lazing", welding or laser recanalization.

An important feature of the PEPS technique is the ability to customizethe application of the polymer to the internal surface of a vessel ororgan as dictated by the particular application. This results in avariety of possible geometries of polymer as well as a variety of forms.These multi-geometry, multi-form polymer structures may be adjusted tocorrespond to particular functions. (FIGS. 1-8)

With particular reference to FIGS. 1-8 the PEPS process may beaffectuated so that the focal application of polymer to the vessel ororgan results in either an amorphous geometry, FIG. 1, stellategeometry, FIG. 2, or spot geometry, FIG. 6. Additional geometries couldinclude a linear feathered polymer strip applied to a particular area ofthe vessel wall as shown in FIG. 3. FIG. 4 shows a large patch ofpolymer which can be sprayed on using a variety of known techniques.Another form of the PEPS application to be utilized in instances, e.g.,where structural stability need be imparted to the vessel would be theporous tubular form shown in FIG. 5. Other types of PEPS applicationswhich would impart structural stability to the vessel would be thespiral form application shown in FIG. 7, or the arcuate (radial, arc)patch as shown in FIG. 8.

Conversely, in cases where the severely denuded lesions have irregularsurfaces with less fibromuscular components, the PEPS process can beused to provide only a thin polymer film to act as a bandage.

The PEPS' process is significantly different and is conceptually anadvance beyond stents and stenting in achieving vessel patency. Stentshave been designed with the underlying primary function of providing arelatively stiff structural support to resist post PTCA, vesselreclosure caused by the vessel's spring-like characteristics. It hasbeen increasingly demonstrated that cellular and biochemical mechanismsas opposed to physical "spring-like" coils, are of a much greatersignificance in preventing vessel reclosure and PEPS addresses thesemechanisms.

The specific object and features of the PEPS process are best understoodby way of illustration with reference to the following examples andfigures.

EXAMPLE 1

The invention may be readily understood through a description of anexperiment performed in vitro using a mock blood vessel made fromtransparent plastic tubing using a heat-balloon type deployment catheterreference to FIG. 17.

The balloon delivery catheter 170 is first positioned in the vessel 171at the area of the occlusion. Before insertion, a polycaprolactonepolymer sleeve 172 containing additives, e.g. to aid X-rayradio-opacity, for drug delivery or to promote surface adhesion, isplaced in a low profile condition surrounding a balloon at the distalend of the delivery catheter 170. The delivery catheter with thepolycaprolactone tube is then inserted balloon end first into the vessel171 and manipulated into position, i.e., the area of the vessel to betreated.

A separate occlusion catheter 173 is employed to restrict "blood" flowthrough the vessel. The distal end of the occlusion catheter 173 isinflated to create a stagnant column of "blood" in the vessel around theballoon delivery catheter and polycaprolactone tube. Saline solution atabout 60°-80° C. is injected through a lumen in the occlusion catheter173 or the delivery catheter 170 in the case of using a catheteraccording to the invention into the area surrounding the deliverycatheter, balloon and polycaprolactone tube. Once the polycaprolactonetube becomes pliable, the delivery catheter balloon is inflated to pushthe polycaprolactone sleeve out against the interior wall therebylocally sealing and/or paving the vessel.

The polycaprolactone expands and/or flows, conforming to the innersurface of the vessel, flowing into and filling in surfaceirregularities thereby creating a "tailored" fit. Further, the deployedinterior surface of the PEPS polymer is smooth providing an increasedvessel (lumen) cross-section diameter and a theologically advantageoussurface with improved blood flow. Upon removal of heated saline solutionthe polymer recrystallizes to provide a paved surface of the vessel wallinterior.

The deployment catheter balloon is then deflated leaving thepolycaprolactone layer in place. The balloon section of the occlusioncatheter is deflated and, blood flow was allowed to return to normal andthe deployment catheter was removed leaving the recrystallizedpolycaprolactone layer in place within the vessel.

Over the course of time the polycaprolactone seal will become coveredwith a proteinaceous biologic thin film coat. Depending upon the exactseal chemical composition, the polymer will then biodegrade, at apredetermined rate and "dissolve" into the bloodstream or be absorbedinto the vessel wall. While in intimate contact with the vessel wall,pharmacological agents if embedded or absorbed in the polycaprolactonewill have a "downstream" effect if released slowly into the bloodstreamor may have a local effect on the blood vessel wall, therebyfacilitating healing of the angioplasty site, controlling or reducingexuberant medial smooth muscle cell proliferation, promoting effectivelesion endothelialyation and reducing lesion thrombogenicity.

EXAMPLE 2

Polycaprolactone in an initial macroporous tubular configuration wasplaced in a low profile form in bovine coronary arteries and caninecarotid arteries. In the process of deployment the vessels werepurposely overextended and sealed through thermal and mechanicaldeformation of the polymer. FIG. 18 shows a cross-section of the polymertube 180 before insertion in the bovine artery, after insertion in theartery 181, and after expansion 182. The initial polymer tube 180, issmaller in diameter than the artery 181. After deployment, the thin filmof polymer 182 can be seen coating the inner surface of the sealedvessel with the vessel remaining erect. The vessel remained dilated toabout 1.5 times the original diameter because of the ability of thepolymer to keep it fixed. FIG. 19 shows a cross-section of the polymerbefore insertion 190 and removed after insertion and reconfiguration 191in a canine artery. This figure clearly shows the stretching andthinning of the polymer wall.

All polymer sealed vessels remained dilated with a thin layer ofmacroporous polymer providing a new barrier surface between the vessellumen and the vessel wall constituents. The unsealed portion of thevessels did not remain dilated.

These examples demonstrate that the PEPS process may if desired providepolymer application with a relatively large degree of surface areacoverage and an effective polymer barrier shield. As such, the polymerbarrier-shield may, if desired, impart sufficient structural stabilityto maintain a selected vessel diameter. The selected final vesseldiameter at which a vessel is sealed is dictated by the particularphysiological variables and therapeutic goals which confront the PEPSuser.

The geometry of the pre and post PEPS application sites may be readilyvaried. PEPS may be used to merely coat an existing vessel or organgeometry. Alternatively, the PEPS process may be used to impartstructural stability to a vessel or organ the geometry of which wasaltered prior to the PEPS application. In addition, the PEPS process mayitself alter the geometry of the vessel or organ by shaping thegeometry. With reference to FIG. 18 this latter process was used toexpand the vessel 181.

A specific and important attribute of the PEPS technique and thepolymers which are employed is the significantly lower degree ofcompliance mismatch or similarities of stiffness (inverse of compliance)between the vessel and the polymer seal as compared to metal stents. Thevessel damage from compliance mismatch discussed above may be eliminatedby the PEPS process utilizing a variety of available polymers.Additionally, compliance mismatch greatly modifies the characteristicsof fluid wave transmission along the vessel with resultant change inlocal flow properties, development of regional change in shear forcesand a subsequent vessel wall hypertrophy which acts to reduce vesselcross-sectional area and reduces blood flow. Further, the substructuralelimination of compliance mismatch of the PEPS technique at firstminimizes and then, upon dissolution eliminates local flow abnormalitiesand up and downstream transition zone hypertrophy associated with metalstenting.

PEPS has the flexibility of being safely and effectively usedprophylactically at the time of initial PTCA in selected patients orbeing incorporated as part of the original dilation procedure as asecond stage prophylactic vessel surface "finishing" process. Forexample, the invasive cardiologist may apply the PEPS technique on awide clinical basis after the first episodes of restenosis. In addition,because the PEPS technique significantly aids in the vascular healingprocess post intervention, it may be readily used prophylactically afterinitial angioplasty prior to any incidence of restenosis. This wouldfree the patient from the risks of repeat intracoronary procedure aswell as those associated with metal stenting.

We claim:
 1. A process for paving or sealing an interior surface of ahollow organ or tissue lumen comprising providing a thermoplasticmaterial in a fluent state in a hollow organ or tissue lumen at alocation requiring structural support, reconfiguring the thermoplasticmaterial to form a layer of thermoplastic material on the interiorsurface, allowing the thermoplastic material to be converted into anon-fluent state in intimate and conforming contact with the tissuesurface thereby paving or sealing the hollow organ or tissue lumen, andallowing the material to remain in intimate and conforming contact withthe interior surface for a period of time effective for said structuralsupport.
 2. A process as in claim 1, comprising using a catheter toposition the thermoplastic material while the thermoplastic material isin a fluent state.
 3. A process as in claim 1, comprising introducing apreshaped thermoplastic material into the hollow organ or tissue lumenin a non-fluent state, rendering the material fluent in the hollow organor tissue lumen, and subsequently applying the material to the interiorsurface.
 4. A process as in claim 3, comprising rendering thethermoplastic material fluent by applying heat to the material.
 5. Aprocess as in claim 4, comprising rendering the thermoplastic materialfluent by applying to the material heated liquid.
 6. A process as inclaim 4, comprising providing the thermoplastic material in the holloworgan or tissue lumen with a catheter, and reconfiguring the materialwith the catheter, the catheter comprising an elongate tubular shafthaving a distal end insertable into a patient and a proximal end adaptedto remain outside of the patient, an expansile member at the distal endof the shaft, and a lumen associated with the shaft that provides fluidcommunication between the proximal end of the shaft and an interiorsurface of the expansile member, and the step of rendering thethermoplastic material fluent involves contacting the material with anexterior wall of the expansile member and delivering a heated liquid tothe interior wall of the expansile member through the lumen.
 7. Aprocess as in claim 4, comprising rendering the thermoplastic materialfluent by applying to the material electromagnetic radiation therebyheating it.
 8. A process as in claim 7, comprising irradiating thethermoplastic material through an optical fiber internal of the cathetershaft.
 9. A process as in claim 8, wherein the optical fiber isconnected to a laser.
 10. A process for paving or sealing an interiorsurface of a hollow organ or a tissue lumen comprising providing abiodegradable thermoplastic material in a fluent state in the holloworgan or tissue lumen, reconfiguring the biodegradable thermoplasticmaterial to form a layer of thermoplastic material on the interiorsurface, and allowing the biodegradable thermoplastic material to beconverted into a non-fluent state in intimate and conforming contactwith the tissue surface.
 11. A process as in claim 10, wherein thethermoplastic material contains a therapeutic agent.
 12. A process as inclaim 10, wherein the thermoplastic material comprises a plurality ofpolymers containing therapeutic agents.
 13. A process as in claim 10,comprising using a catheter to position the thermoplastic material whilethe thermoplastic material is in a fluent state.
 14. A process as inclaim 10, wherein the thermoplastic material contains living cells whichpromote organ regeneration.
 15. A process as in claim 10, furthercomprising allowing the non-fluent thermoplastic material to remain inintimate and conforming contact with the tissue surface for atherapeutically effective period of time.
 16. A process as in claim 10,further comprising allowing the thermoplastic material to remain inintimate and conforming contact with the tissue surface for a period oftime effective to prevent restenosis.
 17. A process as in claim 10,comprising introducing a preshaped thermoplastic material into thehollow organ or tissue lumen in a non-fluent state, rendering thematerial fluent in the hollow organ or tissue lumen, and subsequentlyapplying the material to the interior surface.
 18. A process as in claim17, comprising rendering the thermoplastic material fluent by applyingheat to the material.
 19. A process as in claim 18, comprising renderingthe thermoplastic material fluent by applying to the material heatedliquid.
 20. A process as in claim 18, comprising providing thethermoplastic material in the hollow organ or tissue lumen with acatheter, and reconfiguring the material with the catheter, the cathetercomprising an elongate tubular shaft having a distal end insertable intoa patient and a proximal end adapted to remain outside of the patient,an expansile member at the distal end of the shaft, and a lumenassociated with the shaft that provides fluid communication between theproximal end of the shaft and an interior surface of the expansilemember, and the step of rendering the thermoplastic material fluentinvolves contacting the material with an exterior wall of the expansilemember and delivering a heated liquid to the interior wall of theexpansile member through the lumen.
 21. A process as in claim 18,comprising rendering the thermoplastic material fluent by applying tothe material electromagnetic radiation thereby heating it.
 22. A processas in claim 21, comprising irradiating the thermoplastic materialthrough a optical fiber internal of the catheter shaft.
 23. A process asin claim 22, wherein the optical fiber is connected to a laser.
 24. Aprocess for paving or sealing an interior surface of a hollow organ or atissue lumen comprising providing a thermoplastic material that containsa therapeutic agent in a fluent state in the hollow organ or tissuelumen, reconfiguring the thermoplastic material to form a layer ofthermoplastic material on the interior surface, and allowing thethermoplastic material to be converted into a non-fluent state inintimate and conforming contact with the tissue surface.
 25. A processas in claim 24, wherein the thermoplastic material comprises a pluralityof polymers containing therapeutic agents.
 26. A process as in claim 24,comprising using a catheter to position the thermoplastic material whilethe thermoplastic material is in a fluent state.
 27. A process as inclaim 24, wherein the thermoplastic material contains living cells whichpromote organ regeneration.
 28. A process as in claim 24, furthercomprising allowing the non-fluent thermoplastic material to remain inintimate and conforming contact with the tissue surface for atherapeutically effective period of time.
 29. A process as in claim 24,further comprising allowing the thermoplastic material to remain inintimate and conforming contact with the tissue surface for a period oftime effective to prevent restenosis.
 30. A process as in claim 24,comprising introducing a preshaped thermoplastic material into thehollow organ or tissue lumen in a non-fluent state, rendering thematerial fluent in the hollow organ or tissue lumen, and subsequentlyapplying the material to the interior surface.
 31. A process as in claim30, comprising rendering the thermoplastic material fluent by applyingheat to the material.
 32. A process as in claim 31, comprising renderingthe thermoplastic material fluent by applying to the material heatedliquid.
 33. A process as in claim 31, comprising providing thethermoplastic material in the hollow organ or tissue lumen with acatheter, and reconfiguring the material with the catheter, the cathetercomprising an elongate tubular shaft having a distal end insertable intoa patient and a proximal end adapted to remain outside of the patient,an expansile member at the distal end of the shaft, and a lumenassociated with the shaft that provides fluid communication between theproximal end of the shaft and an interior surface of the expansilemember, and the step of rendering the thermoplastic material fluentinvolves contacting the material with an exterior wall of the expansilemember and delivering a heated liquid to the interior wall of theexpansile member through the lumen.
 34. A process as in claim 31,comprising rendering the thermoplastic material fluent by applying tothe material electromagnetic radiation thereby heating it.
 35. A processas in claim 34, comprising irradiating the thermoplastic materialthrough a optical fiber internal of the catheter shaft.
 36. A process asin claim 35, wherein the optical fiber is connected to a laser.
 37. Aprocess for paving or sealing an interior surface of a hollow organ or atissue lumen comprising providing a thermoplastic material thatcomprises a plurality of polymers containing therapeutic agents in afluent state in the hollow organ or tissue lumen, reconfiguring thethermoplastic material to form a layer of thermoplastic material on theinterior surface, and allowing the thermoplastic material to beconverted into a non-fluent state in intimate and conforming contactwith the tissue surface.
 38. A process as in claim 37, comprising usinga catheter to position the thermoplastic material while thethermoplastic material is in a fluent state.
 39. A process as in claim37, wherein the thermoplastic material contains living cells whichpromote organ regeneration.
 40. A process as in claim 37, furthercomprising allowing the non-fluent thermoplastic material to remain inintimate and conforming contact with the tissue surface for atherapeutically effective period of time.
 41. A process as in claim 37,further comprising allowing the thermoplastic material to remain inintimate and conforming contact with the tissue surface for a period oftime effective to prevent restenosis.
 42. A process as in claim 37,comprising introducing a preshaped thermoplastic material into thehollow organ or tissue lumen in a non-fluent state, rendering thematerial fluent in the hollow organ or tissue lumen, and subsequentlyapplying the material to the interior surface.
 43. A process as in claim42, comprising rendering the thermoplastic material fluent by applyingheat to the material.
 44. A process as in claim 43, comprising renderingthe thermoplastic material fluent by applying to the material heatedliquid.
 45. A process as in claim 43, comprising providing thethermoplastic material in the hollow organ or tissue lumen with acatheter, and reconfiguring the material with the catheter, the cathetercomprising an elongate tubular shaft having a distal end insertable intoa patient and a proximal end adapted to remain outside of the patient,an expansile member at the distal end of the shaft, and a lumenassociated with the shaft that provides fluid communication between theproximal end of the shaft and an interior surface of the expansilemember, and the step of rendering the thermoplastic material fluentinvolves contacting the material with an exterior wall of the expansilemember and delivering a heated liquid to the interior wall of theexpansile member through the lumen.
 46. A process as in claim 43,comprising rendering the thermoplastic material fluent by applying tothe material electromagnetic radiation thereby heating it.
 47. A processas in claim 46, comprising irradiating the thermoplastic materialthrough a optical fiber internal of the catheter shaft.
 48. A process asin claim 47, wherein the optical fiber is connected to a laser.
 49. Aprocess for paving or sealing an interior surface of a hollow organ or atissue lumen comprising providing a thermoplastic material that containsliving cells which promote organ regeneration in a fluent state in thehollow organ or tissue lumen, reconfiguring the thermoplastic materialto form a layer of thermoplastic material on the interior surface, andallowing the thermoplastic material to be converted into a non-fluentstate in intimate and conforming contact with the tissue surface.
 50. Aprocess as in claim 49, comprising using a catheter to position thethermoplastic material while the thermoplastic material is in a fluentstate.
 51. A process as in claim 44, further comprising allowing thenon-fluent thermoplastic material to remain in intimate and conformingcontact with the tissue surface for a therapeutically effective periodof time.
 52. A process as in claim 49, further comprising allowing thethermoplastic material to remain in intimate and conforming contact withthe tissue surface for a period of time effective to prevent restenosis.53. A process as in claim 49, comprising introducing a preshapedthermoplastic material into the hollow organ or tissue lumen in anon-fluent state, rendering the material fluent in the hollow organ ortissue lumen, and subsequently applying the material to the interiorsurface.
 54. A process as in claim 53, comprising rendering thethermoplastic material fluent by applying heat to the material.
 55. Aprocess as in claim 54, comprising rendering the thermoplastic materialfluent by applying to the material heated liquid.
 56. A process as inclaim 54, comprising providing the thermoplastic material in the holloworgan or tissue lumen with a catheter, and reconfiguring the materialwith the catheter, the catheter comprising an elongate tubular shafthaving a distal end insertable into a patient and a proximal end adaptedto remain outside of the patient, an expansile member at the distal endof the shaft, and a lumen associated with the shaft that provides fluidcommunication between the proximal end of the shaft and an interiorsurface of the expansile member, and the step of rendering thethermoplastic material fluent involves contacting the material with anexterior wall of the expansile member and delivering a heated liquid tothe interior wall of the expansile member through the lumen.
 57. Aprocess as in claim 54, comprising rendering the thermoplastic materialfluent by applying to the material electromagnetic radiation therebyheating it.
 58. A process as in claim 57, comprising irradiating thethermoplastic material through a optical fiber internal of the cathetershaft.
 59. A process as in claim 58, wherein the optical fiber isconnected to a laser.